Autor: |
Korkus E; Faculty of Biotechnology and Food Sciences, Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland. edyta.gendaszewska-darmach@p.lodz.pl., Szustak M; Faculty of Biotechnology and Food Sciences, Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland. edyta.gendaszewska-darmach@p.lodz.pl., Madaj R; Division of Bioorganic Chemistry Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza, 112, 90-363 Lodz, Poland.; Institute of Evolutionary Biology, Faculty of Biology, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089, Warsaw, Poland., Chworos A; Division of Bioorganic Chemistry Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza, 112, 90-363 Lodz, Poland., Drzazga A; Faculty of Biotechnology and Food Sciences, Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland. edyta.gendaszewska-darmach@p.lodz.pl., Koziołkiewicz M; Faculty of Biotechnology and Food Sciences, Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland. edyta.gendaszewska-darmach@p.lodz.pl., Dąbrowski G; Faculty of Food Sciences, Chair of Plant Food Chemistry and Processing, University of Warmia and Mazury in Olsztyn, Pl. Cieszyński 1, 10-957 Olsztyn, Poland., Czaplicki S; Faculty of Food Sciences, Chair of Plant Food Chemistry and Processing, University of Warmia and Mazury in Olsztyn, Pl. Cieszyński 1, 10-957 Olsztyn, Poland., Konopka I; Faculty of Food Sciences, Chair of Plant Food Chemistry and Processing, University of Warmia and Mazury in Olsztyn, Pl. Cieszyński 1, 10-957 Olsztyn, Poland., Gendaszewska-Darmach E; Faculty of Biotechnology and Food Sciences, Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland. edyta.gendaszewska-darmach@p.lodz.pl. |
Abstrakt: |
Dietary trans -palmitoleic acid ( trans 16:1n-7, t POA), a biomarker for high-fat dairy product intake, has been associated with a lower risk of type 2 diabetes mellitus (T2DM) in some cross-sectional and prospective epidemiological studies. Here, we investigated the insulin secretion-promoting activity of t POA and compared them with the effects evoked by the cis -POA isomer ( c POA), an endogenous lipokine biosynthesized in the liver and adipose tissue, and found in some natural food sources. The debate about the positive and negative relationships of those two POA isomers with metabolic risk factors and the underlying mechanisms is still going on. Therefore, we examined the potency of both POA isomers to potentiate insulin secretion in murine and human pancreatic β cell lines. We also investigated whether POA isomers activate G protein-coupled receptors proposed as potential targets for T2DM treatment. We show that t POA and c POA augment glucose-stimulated insulin secretion (GSIS) to a similar extent; however, their insulin secretagogue activity is associated with different signaling pathways. We also performed ligand docking and molecular dynamics simulations to predict the preferred orientation of POA isomers and the strength of association between those two fatty acids and GPR40, GPR55, GPR119, and GPR120 receptors. Overall, this study provides insight into the bioactivity of t POA and c POA toward selected GPCR functions, indicating them as targets responsible for the insulin secretagogue action of POA isomers. It reveals that both t POA and c POA may promote insulin secretion and subsequently regulate glucose homeostasis. |